Association between combination COVID-19-influenza vaccination and long COVID in middle-aged and older Europeans: A cross-sectional study.

The potential impact of combined COVID-19 and influenza vaccination on long COVID remains uncertain. In the present cross-sectional study, we aimed to investigate the plausible association between them in middle-aged and older Europeans based on the Survey of Health, Ageing, and Retirement in Europe (SHARE). A total of 1910 participants were recruited in the analyses. The study outcome was long COVID. Participants were divided into 4 groups through the self-reported status of COVID-19 and influenza vaccination. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. 1397 participants experienced long COVID. After multivariable adjustment, those vaccinated with neither COVID-19 nor influenza vaccine had higher risk of long COVID (OR, 1.72; 95% CI, 1.26-2.35) compared to those vaccinated with both vaccines. Furthermore, adding the 4 statuses of COVID-19 vaccination/influenza vaccination to conventional risk model improved risk reclassification for long COVID (continuous net reclassification improvement was 16.26% [p = .003], and integrated discrimination improvement was 0.51% [p = .005]). No heterogeneity was found in the subgroup analyses (all p-interaction ≥0.05). Our study might provide a strategy for people aged 50 and over to reduce the occurrence of long COVID, that is, to combine the use of the COVID-19 vaccine and influenza vaccines.

Experiencing art creation as a therapeutic intervention to relieve anxiety - a case study of a university's ceramic art course.

Background: University students are anxiety prone. Due to their changing their social roles, the proportion of university students with anxiety is relatively high. In this study, using the simple random sampling, we surveyed 53 university students, including sophomores, juniors, and seniors. Aims: This paper examines the relationship between art creation and anxiety. Methods: This study uses the Self-Assessment Anxiety Scale (SAS). The test form measures the presence and extent of their anxiety problems through a series of questions. We tested the effects of an art creation process on SAS scores and suggest best practices for course settings and teaching methods for art-related subjects. Results: Art therapy intervention reduced anxiety. The most effective technique was found to be slapping the clay board during the creation process. Other actions relieved anxiety as well. Results suggest that the art creation process is an application of art therapy effective in relieving anxiety in university students. Conclusion: Key actions in the process of creating art are closely related to the treatment approaches used in art therapy interventions. This has the potential to not only improve mental health, but also to promote the health and well-being of students. Implications for future research: Rapid societal changes increasing competition for employment creates work and life pressures. University students face challenges with learning, peer competition, and employment, often resulting in anxiety. A diversified curriculum can alleviate anxiety through proper curricular planning and design. Based on this, the university's arts courses should be able to study how to improve and optimize the existing teaching and learning outcomes and can be integrated with the university's general education curriculum planning. Through appropriate teaching content and learning methods, the courses of university general education can play a role in reducing students' anxiety and promote physical and mental health, thus contributing to sustainable development of the society.

[The dynamic monitoring of gastric residual volume by ultrasound was used to guide the early nutritional treatment of patients with severe mechanical ventilation to gradually achieve the standard].

OBJECTIVE: To explore the application value of dynamic monitoring of gastric residual volume (GRV) in achieving different target energy in severe mechanical ventilation patients. METHODS: A prospective randomized controlled study was conducted. Forty-two patients with mechanical ventilation admitted to the department of critical care medicine of General Hospital of Ningxia Medical University from July to December 2022 were enrolled. According to the random number table method, patients were divided into GRV guided enteral nutrition by traditional gastric juice pumpback method (control group, 22 patients) and GRV guided enteral nutrition by bedside ultrasound (test group, 20 patients). General data were collected from both groups, and clinical indicators such as hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), neutrophil percentage (Neut%), procalcitonin (PCT), absolute lymphocytes (LYM), prealbumin (PA), and retinol-binding protein (RBP) were dynamically observed. Inflammation, infection, immunity, nutritional indicators, and the incidence of reflux/aspiration, ventilator-associated pneumonia (VAP) were compared between the two groups, and further compared the proportion of patients with respectively to reach the target energy 25%, 50%, and 70% on days 1, 3, and 5 of initiated enteral nutrition. RESULTS: (1) There were no significant differences in gender, age, body mass index (BMI), duration of mechanical ventilation, and acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), severe nutritional risk score (NUTRIC) at admission between the two groups, indicating comparability. (2) On day 1 of initiated enteral nutrition, there were no significant differences in infection, inflammation, immunity and nutrition indicators between the two groups. On day 3 of initiated enteral nutrition, the hs-CRP in the test group was lower than that control group, LYM and PA were higher than those control group [hs-CRP (mg/L): 129.60±75.18 vs. 185.20±63.74, LYM: 1.00±0.84 vs. 0.60±0.41, PA (mg/L): 27.30±3.66 vs. 22.30±2.55, all P < 0.05]. On day 5 of initiated enteral nutrition, the hs-CRP, Neut%, PCT in the test group were lower than those control group, LYM and PA were higher than those control group [hs-CRP (mg/L): 101.70±54.32 vs. 148.40±36.35, Neut%: (85.50±7.66)% vs. (92.90±6.01)%, PCT (µg/L): 0.7 (0.3, 2.7) vs. 3.6 (1.2, 7.5), LYM: 1.00±0.68 vs. 0.50±0.38, PA (mg/L): 27.10±4.57 vs. 20.80 ± 3.51, all P < 0.05]. There were no significantly differences in IL-6 and RBP between the two groups at different time points. (3) The proportion of 50% and 70% of achieved target energy in the test group on day 3, day 5 of initiated enteral nutrition were higher than those of the control group (70.0% vs. 36.4%, 70.0% vs. 36.4%, both P < 0.05). (4) The incidence of reflux/aspiration and VAP in the test group on day 5 of initiated enteral nutrition were significantly lower than those control group (incidence of reflux/aspiration: 5.0% vs. 28.6%, incidence of VAP: 10.0% vs. 36.4%, both P < 0.05). CONCLUSIONS: Dynamic monitoring of GRV by bedside ultrasound can accurately improve the proportion of 50% of achieved target energy on day 3 and 75% on day 5 in severe mechanical ventilation patients, improve the patient's inflammation, immune and nutritional status, and can prevent the occurrence of reflux/aspiration and VAP.

Bile acids inhibit ferroptosis sensitivity through activating farnesoid X receptor in gastric cancer cells.

BACKGROUND: Gastric cancer (GC) is associated with high mortality rates. Bile acids (BAs) reflux is a well-known risk factor for GC, but the specific mechanism remains unclear. During GC development in both humans and animals, BAs serve as signaling molecules that induce metabolic reprogramming. This confers additional cancer phenotypes, including ferroptosis sensitivity. Ferroptosis is a novel mode of cell death characterized by lipid peroxidation that contributes universally to malignant progression. However, it is not fully defined if BAs can influence GC progression by modulating ferroptosis. AIM: To reveal the mechanism of BAs regulation in ferroptosis of GC cells. METHODS: In this study, we treated GC cells with various stimuli and evaluated the effect of BAs on the sensitivity to ferroptosis. We used gain and loss of function assays to examine the impacts of farnesoid X receptor (FXR) and BTB and CNC homology 1 (BACH1) overexpression and knockdown to obtain further insights into the molecular mechanism involved. RESULTS: Our data suggested that BAs could reverse erastin-induced ferroptosis in GC cells. This effect correlated with increased glutathione (GSH) concentrations, a reduced GSH to oxidized GSH ratio, and higher GSH peroxidase 4 (GPX4) expression levels. Subsequently, we confirmed that BAs exerted these effects by activating FXR, which markedly increased the expression of GSH synthetase and GPX4. Notably, BACH1 was detected as an essential intermediate molecule in the promotion of GSH synthesis by BAs and FXR. Finally, our results suggested that FXR could significantly promote GC cell proliferation, which may be closely related to its anti-ferroptosis effect. CONCLUSION: This study revealed for the first time that BAs could inhibit ferroptosis sensitivity through the FXR-BACH1-GSH-GPX4 axis in GC cells. This work provided new insights into the mechanism associated with BA-mediated promotion of GC and may help identify potential therapeutic targets for GC patients with BAs reflux.

Changes in inflammatory markers and efficacy analysis of continuous subcutaneous insulin infusion in senior patients with type 2 diabetes mellitus hospitalized with community-acquired pneumonia: a randomized controlled trial.

OBJECTIVE: The purpose of this study is to analyze the changes in inflammatory markers and efficacy in the treatment of senior patients with type 2 diabetes mellitus (T2DM) and community-acquired pneumonia with continuous subcutaneous insulin infusion (CSII). METHODS: A total of 105 senior patients with T2DM and community-acquired pneumonia, were randomly divided into two groups, viz., treatment group and control group-52 patients in the treatment group were treated with CSII, and 53 patients in the control group with multiple daily insulin injections (MDI). The changes in fasting blood glucose, postprandial blood glucose, total number of white blood cells, neutrophils, percentage of neutrophils, lymphocytes, percentage of lymphocytes, C-reactive protein, serum amyloid A, procalcitonin, interleukin-6 indexes, and the improvement in clinical outcome between the two groups were compared on the 5th and the 10th day of treatment. RESULTS: In the treatment group, there were 52 patients with an average age of (73.7 ± 8.5) years, which included 28 males and 24 females. In the control group, there were 53 patients, with 27 males and 26 females, with an average age of (74.8 ± 8.8) years. On the 5th and the 10th day of the treatment, the fasting blood glucose, postprandial blood glucose, total number of white blood cells, neutrophils, percentage of neutrophils, lymphocytes, percentage of lymphocytes, C-reactive protein, serum amyloid A, procalcitonin and interleukin-6 of the treatment group were better than that of the control group (P < 0.05). The use of CSII was associated with a higher probability of a prompt recovery (P < 0.05). CONCLUSION: The administration of CSII in the treatment of senior patients with T2DM and community-acquired pneumonia can effectively control fasting and postprandial blood glucose, significantly reduce the levels of inflammatory markers, and improve infection treatment efficacy.

Diagnosis, Treatment, and Associated Factors Among Patients with HCV Infection - Jiangsu Province, China, 2004-2020.

What is already known on this topic?: The global efforts to address the hepatitis C virus (HCV) are progressing, but there are still significant gaps in the diagnosis and treatment of HCV, leading to an increasing number of deaths related to HCV. What is added by this report?: An extensive investigation was conducted to assess HCV RNA diagnosis, treatment uptake, and associated factors among individuals infected with HCV within Jiangsu Province. The study encompassed a large geographical area and utilized a substantial sample size. What are the implications for public health practice?: Implementing focused interventions to improve the timely diagnosis of HCV RNA and increase the uptake of HCV treatment could effectively reduce the future burden of HCV-related health problems, deaths, and healthcare expenses. This is essential for achieving the global target of eliminating hepatitis C.

Congenital leukemia: A case report and review of literature.

BACKGROUND: Acute leukemia in newborns is also known as neonatal or congenital leukemia (CL) and is a rare disease with an incidence rate of 1-5 per 1000000 live births. After birth, infants with CL exhibit infiltrative cutaneous nodules, hepatosplenomegaly, thrombocytopenia, and immature leukocytes in the peripheral blood. These symptoms are frequently accompanied by congenital abnormalities including trisomy 21, trisomy 9, trisomy 13, or Turner syndrome. Despite significant advances in disease management, the survival rate is approximately 25% at 2 years. CASE SUMMARY: Here, we document a case of trisomy 21-related acute myeloid leukemia (AML) in a female neonate. The baby was sent to the neonatal intensive care unit because of anorexia, poor responsiveness, and respiratory distress. She was diagnosed with AML based on bone marrow aspiration and immunophenotyping. Genetic sequencing identified a mutation in the GATA1 gene. After receiving the diagnosis, the parents decided against medical care for their child, and the baby died at home on day 9 after birth. CONCLUSIONS: The newborn infant was diagnosed with trisomy 21-related AML. Genetic sequencing identified a mutation in the GATA1 gene. The parents abandoned medical treatment for their infant after receiving the diagnosis, and the infant died at home on the 9th day after birth.

The efficacy and safety of immune checkpoint inhibitors for patients with EGFR-mutated non-small cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy: A systematic review and network meta-analysis.

BACKGROUND: Non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR)-mutated who progressed on EGFR tyrosine-kinase inhibitor (EGFR-TKI) therapy have limited therapeutic options. There is still no consensus on the role of immune checkpoint inhibitors (ICIs) in NSCLC with EGFR mutations. METHODS: We did a network meta-analysis (NMA) with a systematic literature search on PubMed, Embase, Web of Science, and The Cochrane Library. We included all phase II and III randomized controlled trials (RCTs), non-randomized controlled trials (Non-RCTs), and retrospective studies. Progression-free survival (PFS) and overall survival (OS) were assessed through hazard ratios (HR). Objective response rate (ORR) and adverse events (AEs) were assessed through odds ratio (OR) and relative risk (RR), respectively. R software was used to compare the outcomes of different treatments by Bayesian NMA. FINDINGS: We identified 1835 published results and 17 studies were included ultimately. A total of 2085 patients were included and accepted the following six treatments: ICIs plus chemotherapy (ICIs+Chemo), chemotherapy (Chemo), ICIs monotherapy (ICIs), ICIs plus chemotherapy and antiangiogenic therapy (ICIs+Chemo+Antiangio), antiangiogenic therapy plus chemotherapy (Antiangio+Chemo), ICIs plus antiangiogenic therapy (ICIs+Antiangio). ICIs+Chemo+Antiangio was associated with longer PFS and OS, as well as higher ORR (surface under the cumulative ranking curve [SUCRA], 96%, 90%, 91%). ICIs conferred the safety profile in terms of any-grade AEs, grade greater than or equal to 3 AEs and any grade leading to treatment discontinuation occurred AEs (SUCRA, 99%, 68%, 94%). INTERPRETATION: ICIs+Chemo+Antiangio brings the greatest survival benefit in NSCLC patients with EGFR mutations who progressed on EGFR-TKI therapy, even for whom with baseline brain metastases. Compared with chemotherapy, ICIs has a low incidence of AEs and a benefit in OS.

Low-dose benzo[a]pyrene exposure induces hepatic lipid deposition through LCMT1/PP2Ac-mediated autophagy inhibition.

Non-alcoholic fatty liver disease (NAFLD) is a progressive disorder of liver metabolism and has become the most common chronic liver disease worldwide. Benzo[a]pyrene (BaP) is recognized as a potent carcinogen, but the effect of low-dose BaP on the development of NAFLD has not been well-studied, and its molecular mechanism is still unknown. In this study, we demonstrated that low-dose BaP induced hepatic steatosis in a mouse model with a notable increase in hepatic lipid content. Interestingly, mRNA expression of genes related to fatty acids uptake or synthesis was not significantly altered after BaP exposure. Instead, we found that low-dose BaP promoted lipid deposition in primary mouse hepatocytes by inhibiting autophagy, which was regulated through Leucine carboxyl methyltransferase-1 (LCMT1) mediated Protein Phosphatases 2A subunit C (PP2Ac) methylation. The role of LCMT1 in BaP-induced steatosis was further validated in a liver-specific lcmt1 knockout (L-LCMT1 KO) mouse model. In this study, we provided evidence to support a novel mechanism by which BaP induces the development of hepatic steatosis through PP2Ac mediated autophagy inhibition. These findings provided new insight into the pathogenesis of NAFLD induced by environmental exposure to low-dose BaP.

Thioridazine protects against disturbed flow-induced atherosclerosis by inhibiting RhoA/YAP-mediated endothelial inflammation.

Atherosclerotic diseases remain the leading cause of adult mortality and impose heavy burdens on health systems globally. Our previous study found that disturbed flow enhanced YAP activity to provoke endothelial activation and atherosclerosis, and targeting YAP alleviated endothelial inflammation and atherogenesis. Therefore, we established a luciferase reporter assay-based drug screening platform to seek out new YAP inhibitors for anti-atherosclerotic treatment. By screening the FDA-approved drug library, we identified that an anti-psychotic drug thioridazine markedly suppressed YAP activity in human endothelial cells. Thioridazine inhibited disturbed flow-induced endothelial inflammatory response in vivo and in vitro. We verified that the anti-inflammatory effects of thioridazine were mediated by inhibition of YAP. Thioridazine regulated YAP activity via restraining RhoA. Moreover, administration of thioridazine attenuated partial carotid ligation- and western diet-induced atherosclerosis in two mouse models. Overall, this work opens up the possibility of repurposing thioridazine for intervention of atherosclerotic diseases. This study also shed light on the underlying mechanisms that thioridazine inhibited endothelial activation and atherogenesis via repression of RhoA-YAP axis. As a new YAP inhibitor, thioridazine might need further investigation and development for the treatment of atherosclerotic diseases in clinical practice.

Grip strength affects the association between platelet count and disability-free survival: Evidence from the China Health and Retirement Longitudinal Study.

BACKGROUND AND AIMS: Previous studies found elevated platelet count (PLT), especially long-term persist high or increased PLT was associated with less likelihood disability-free survival (DFS). However, whether grip strength affects the relationship between them is still not elucidated. METHODS: A total of 6252 participants were recruited in the analysis based on the China Health and Retirement Longitudinal Study. The primary outcome was DFS, evaluated by a composite endpoint based on the first occurrence of either disability (having difficulty in at least one of the 6 activities of daily living: namely, dressing, bathing, continence, eating, getting into or out of bed, and toileting) or all-cause mortality. RESULTS: The association of PLT with primary outcome was significantly modified by grip strength (pinteraction = 0.022). The rates of primary outcome were significantly lower among participants with lower baseline PLT in participants with normal grip strength (multivariable odds ratio [OR], 0.67; 95% confidence interval [CI], 0.54-0.84; ptrend < 0.001), but not in those with low grip strength (multivariable OR, 1.70; 95% CI, 0.88-3.15; ptrend = 0.135), for the lowest quartile vs the highest quartile. Adding baseline PLT (quartiles or continuous) to a model containing conventional risk factors significantly improved risk reclassification for primary outcome among those with normal grip strength (most of p < 0.05). CONCLUSION: An inverse dose-response association of PLT with DFS was found among participants with normal grip strength, but not among those with low grip strength. Low grip strength might weaken the benefit of low PLT on DFS among middle-aged and older Chinese.

Hepatic leucine carboxyl methyltransferase 1 (LCMT1) contributes to high fat diet-induced glucose intolerance through regulation of glycogen metabolism.

Impaired glucose regulation is one of the most important risk factors for type 2 diabetes mellitus (T2DM) and cardiovascular diseases, which have become a major public health issue worldwide. Dysregulation of carbohydrate metabolism in liver has been shown to play a critical role in the development of glucose intolerance but the molecular mechanism has not yet been fully understood. In this study, we investigated the role of hepatic LCMT1 in the regulation of glucose homeostasis using a liver-specific LCMT1 knockout mouse model. The hepatocyte-specific deletion of LCMT1 significantly upregulated the hepatic glycogen synthesis and glycogen accumulation in liver. We found that the liver-specific knockout of LCMT1 improved high fat diet-induced glucose intolerance and insulin resistance. Consistently, the high fat diet-induced downregulation of glucokinase (GCK) and other important glycogen synthesis genes were reversed in LCMT1 knockout liver. In addition, the expression of GCK was significantly upregulated in MIHA cells treated with siRNA targeting LCMT1 and improved glycogen synthesis. In this study, we provided evidences to support the role of hepatic LCMT1 in the development of glucose intolerance induced by high fat diet and demonstrated that inhibiting LCMT1 could be a novel therapeutic strategy for the treatment of glucose metabolism disorders.

Spatiotemporal Changes in Pulmonary Tuberculosis Incidence in a Low-Epidemic Area of China in 2005-2020: Retrospective Spatiotemporal Analysis.

BACKGROUND: In China, tuberculosis (TB) is still a major public health problem, and the incidence of TB has significant spatial heterogeneity. OBJECTIVE: This study aimed to investigate the temporal trends and spatial patterns of pulmonary tuberculosis (PTB) in a low-epidemic area of eastern China, Wuxi city, from 2005 to 2020. METHODS: The data of PTB cases from 2005 to 2020 were obtained from the Tuberculosis Information Management System. The joinpoint regression model was used to identify the changes in the secular temporal trend. Kernel density analysis and hot spot analysis were used to explore the spatial distribution characteristics and clusters of the PTB incidence rate. RESULTS: A total of 37,592 cases were registered during 2005-2020, with an average annual incidence rate of 34.6 per 100,000 population. The population older than 60 years had the highest incidence rate of 59.0 per 100,000 population. In the study period, the incidence rate decreased from 50.4 to 23.9 per 100,000 population, with an average annual percent change of -4.9% (95% CI -6.8% to -2.9%). The incidence rate of pathogen-positive patients increased during 2017-2020, with an annual percent change of 13.4% (95% CI 4.3%-23.2%). The TB cases were mainly concentrated in the city center, and the incidence of hot spots areas gradually changed from rural areas to urban areas during the study period. CONCLUSIONS: The PTB incidence rate in Wuxi city has been declining rapidly with the effective implementation of strategies and projects. The populated urban centers will become key areas of TB prevention and control, especially in the older population.

Hardness Distribution of Al2050 Parts Fabricated Using Additive Friction Stir Deposition.

The solid-state additive friction stir deposition (AFSD) process is a layer-by-layer metal 3D-printing technology. In this study, AFSD is used to fabricate Al-Cu-Li 2050 alloy parts. The hardness values for various regions of the as-deposited built parts are measured, and the results are contrasted with those of the feedstock material. The as-fabricated Al2050 parts are found to have a unique hardness distribution due to the location-specific variations in the processing temperature profile. The XRD results indicate the presence of the secondary phases in the deposited parts, and EDS mapping confirms the formation of detectable alloying particles in the as-deposited Al2050 matrix. The AFSD thermal-mechanical process causes the unique hardness distribution and the reduced microhardness level in the AFSD components, in contrast to those of the feedstock material.

CircFhit Modulates GABAergic Synaptic Transmission via Regulating the Parental Gene Fhit Expression in the Spinal Dorsal Horn in a Rat Model of Neuropathic Pain.

Effective treatments for neuropathic pain are lacking due to our limited understanding of the mechanisms. The circRNAs are mainly enriched in the central nervous system. However, their function in various physiological and pathological conditions have yet to be determined. Here, we identified circFhit, an exon-intron circRNA expressed in GABAergic neurons, which reduced the inhibitory synaptic transmission in the spinal dorsal horn to mediate spared nerve injury-induced neuropathic pain. Moreover, we found that circFhit decreased the expression of GAD65 and induced hyperexcitation in NK1R+ neurons by promoting the expression of its parental gene Fhit in cis. Mechanistically, circFhit was directly bound to the intronic region of Fhit, and formed a circFhit/HNRNPK complex to promote Pol II phosphorylation and H2B monoubiquitination by recruiting CDK9 and RNF40 to the Fhit intron. In summary, we revealed that the exon-intron circFhit contributes to GABAergic neuron-mediated NK1R+ neuronal hyperexcitation and neuropathic pain via regulating Fhit in cis.

Elevated expression of TNFRSF4 impacts immune cell infiltration and gene mutation in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly heterogeneous disease, which makes prognostic prediction challenging.We aimed to investigate association of TNFRSF4 expression with the immune infiltration and gene mutation in HCC. METHODS: In this study, the expression profiles and corresponding clinical data of HCC patients were downloaded from the Cancer Genome Atlas (TCGA) database.Kaplan-Meier and Cox regression were used to evaluate the clinical value of TNFRSF4. ESTIMATE and CIBERSORT algorithms were applied to investigate the infiltration ratio of 22 immune cells. The WGCNA and LASSO COX algorithms were performed, establishing a prognostic risk model that was then validated by HCC samples from GEO. Finally, the effects on gene mutation occurring in HCC patients of TNFRSF4 expression and risk score were appraised. RESULTS: In HCC tissues, it was found the TNFRSF4 expression profile was significantly different with age, gender, tumor grade, disease stage, prominently affecting the survival outcome and prognosis of patients. Univariate and multivariate COX regression analysis suggested that TNFRSF4 was an independent prognostic marker. Samples of high/low expression of TNFRSF4 were screened for differential genes, and then the WGCNA and LASSO COX constructed a 13-gene signature, excellently dividing samples into hign/low risk groups. Compared with the low-risk group, the overall survival (OS) of high-risk group was markedly lower, with P< 0.0001. By ROC curve analysis, the predictive ability of the 13-gene signature was further confirmed. Both the high/low TNFRSF4 expression and the high/low risk score were demonstrated to exert effects on the frequency of gene mutation in HCC. CONCLUSIONS: As an independent prognostic marker of HCC, TNFRSF4 was found simultaneously to affect the immune infiltration of cells and the frequency of gene mutations.

Effects of Printing Layer Orientation on the High-Frequency Bending-Fatigue Life and Tensile Strength of Additively Manufactured 17-4 PH Stainless Steel.

In this paper, small blocks of 17-4 PH stainless steel were manufactured via extrusion-based bound powder extrusion (BPE)/atomic diffusion additive manufacturing (ADAM) technology in two different orientations. Ultrasonic bending-fatigue and uniaxial tensile tests were carried out on the test specimens prepared from the AM blocks. Specifically, a recently-introduced small-size specimen design is employed to carry out time-efficient fatigue tests. Based on the results of the testing, the stress-life (S-N) curves were created in the very high-cycle fatigue (VHCF) regime. The effects of the printing orientation on the fatigue life and tensile strength were discussed, supported by fractography taken from the specimens' fracture surfaces. The findings of the tensile test and the fatigue test revealed that vertically-oriented test specimens had lower ductility and a shorter fatigue life than their horizontally-oriented counterparts. The resulting S-N curves were also compared against existing data in the open literature. It is concluded that the large-sized pores (which originated from the extrusion process) along the track boundaries strongly affect the fatigue life and elongation of the AM parts.

Diosmetin inhibits subchondral bone loss and indirectly protects cartilage in a surgically-induced osteoarthritis mouse model.

Osteoarthritis (OA) is a common degenerative disease characterized by articular cartilage destruction, subchondral bone remodeling, ectopic osteophyte formation and synovitis. It is now recognized that the integrity of the underlying subchondral bone is crucial for the maintenance of the overlying articular cartilage. Therapeutic agents that can prevent subchondral bone loss are demonstrate potential in the prevention and treatment of OA. Diosmetin (DIOS; 3',5,7 -trihydroxy-4'-methoxy flavone), a natural flavonoid, has been shown to exert anti-oxidative, anti-inflammatory, anti-apoptotic and anticancer properties. In this study, we found that diosmetin suppressed the DMM-induced subchondral bone loss and reduced subsequent cartilage degradation in vivo. Cellular-based assays showed that diosmetin inhibited RANKL-induced osteoclast formation and bone resorption,but did not affect IL-1ß-induced chondrocyte hypertrophy. Biochemical analyses demonstrated that the anti-osteoclastic effect of diosmetin was at least in part due to the suppression of RANKL-induced activation of the ERK, p38, and JNK MAPK signaling pathways. Collectively, our results show that diosmetin have potential as a therapeutic agent the treatment of abnormal subchondral bone loss and cartilage degradation associated with the onset of OA.

Efficacy of Pretreatment with Lycium barbarum Polysaccharide in Various Doses in Influencing Splenic Immunity and Prognosis of Sepsis in Rats.

Objective: Sepsis, showing high mortality, is a lethal dysfunction of organs caused by an infection-induced disorder in the host response. It has complicated pathogenesis, which has not yet been elucidated completely. Recently, the principal factors causing pathogenesis and even death in sepsis patients are imbalance in inflammatory response and immunosuppression occurring when the host is challenged by infection. Previous studies found that Lycium barbarum polysaccharide (LBP) worked well in enhancing immunity. This study aims at exploring the efficacy of pretreatment with LPB in regulating splenic immunity during the pathogenesis of sepsis induced by cecum ligation perforation (CLP) in rats. Methods: This research established the cecum ligation perforation rat model. Using immunohistochemistry and flow cytometry, the effects of Lycium barbarum polysaccharide in various doses in influencing splenic immunity and prognosis of sepsis induced by cecum ligation perforation in rats were examined. Results: This study showed that LBP lowered the 72-hour mortality of sepsis rats induced by CLP, relieved systemic inflammation, improved the ratio of T-cell subgroups positive in CD3+, CD4+, or CD8+ and expression of HLA-DR protein, and repaired damage to splenic tissue, implying its efficacy in enhancing the immunity of sepsis rats induced by CLP. Conclusions: LBP may ameliorate clinical symptoms of rats with cecum ligation perforation, improve cellular immunity in the spleen, and treat sepsis so as to provide a theoretical basis for the pathogenesis and development of sepsis as well as its diagnosis and treatment, and offer scientific proof for the development and utilization of LBP applied to critical diseases.

Construction and evaluation of a prognostic risk model of tumor metastasis-related genes in patients with non-small cell lung cancer.

BACKGROUND: Lung cancer is a high-incidence cancer, and it is also the most common cause of cancer death worldwide. 80-85% of lung cancer cases can be classified as non-small cell lung cancer (NSCLC). METHODS: NSCLC transcriptome data and clinical information were downloaded from the TCGA database and GEO database. Firstly, we analyzed and identified the differentially expressed genes (DEGs) between non-metastasis group and metastasis group of NSCLC in the TCGA database, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) were consulted to explore the functions of the DEGs. Thereafter, univariate Cox regression and LASSO Cox regression algorithms were applied to identify prognostic metastasis-related signature, followed by the construction of the risk score model and nomogram for predicting the survival of NSCLC patients. GSEA analyzed that differentially expressed gene-related signaling pathways in the high-risk group and the low-risk group. The survival of NSCLC patients was analyzed by the Kaplan-Meier method. ROC curve was plotted to evaluate the accuracy of the model. Finally, the GEO database was further applied to verify the metastasis­related prognostic signature. RESULTS: In total, 2058 DEGs were identified. GO functions and KEGG pathways analysis results showed that the DEGs mainly concentrated in epidermis development, skin development, and the pathway of Neuro active ligand -receptor interaction in cancer. A six-gene metastasis-related risk signature including C1QL2, FLNC, LUZP2, PRSS3, SPIC, and GRAMD1B was constructed to predict the overall survival of NSCLC patients. The reliability of the gene signature was verified in GSE13213. The NSCLC patients were grouped into low-risk and high-risk groups based on the median value of risk scores. And low-risk patients had lower risk scores and longer survival time. Univariate and multivariate Cox regression verified that this signature was an independent risk factor for NSCLC. CONCLUSION: Our study identified 6 metastasis biomarkers in the NSCLC. The biomarkers may contribute to individual risk estimation, survival prognosis.